Disease relevance of Nsdhl

• Human homologue of the murine bare patches/striated gene is not mutated in incontinentia pigmenti type 2 [1].
• We conclude that Str mouse is a good model to get new insights in the pathogenesis of ectodermal dysplasias and X linked male lethality in humans [2].
• Transgenic mice carrying the bel region of human foamy retrovirus (HFV) under transcriptional control of its own long terminal repeat expressed the transgene in their central nervous systems and in smooth and striated muscle tissues [3].
• Mutations in lamins A and C, nuclear intermediate-filament proteins in nearly all somatic cells, cause a variety of diseases that primarily affect striated muscle, adipocytes, or peripheral nerves or cause features of premature aging [4].
• Cypher knockout mice display a severe form of congenital myopathy and die postnatally from functional failure in multiple striated muscles [5].

High impact information on Nsdhl

• The Bpa gene has recently been identified and encodes a protein with homology to 3beta-hydroxysteroid dehydrogenases that functions in one of the later steps of cholesterol biosynthesis [6].
• Our results demonstrate that Bpa and Str are allelic mutations and identify the first mammalian locus associated with an X-linked dominant, male-lethal phenotype [7].
• Here we report mutations in one of these genes, Nsdhl, encoding an NAD(P)H steroid dehydrogenase-like protein, in two independent Bpa and three independent Str alleles [7].
• The gene mutated in bare patches and striated mice encodes a novel 3beta-hydroxysteroid dehydrogenase [7].
• The transgene is transcribed in peritoneal cells, as well as in eyes and infiltrated striated muscle [8].

Chemical compound and disease context of Nsdhl

• This report describes a congenital myopathy and major loss of thymic lymphocytes in ankyrin-B (-/-) mice as well as dramatic alterations in intracellular localization of key components of the Ca(2+) homeostasis machinery in ankyrin-B (-/-) striated muscle and thymus [9].
• P19 embryonal carcinoma cells are multipotential stem cells that differentiate into striated muscle as well as some other cell types when aggregated and exposed to dimethyl sulfoxide (DMSO) [10].
• CI-934 was the most potent quinolone in infections induced by Streptococcus pyogenes and Str. pneumoniae [11].
• In aerobic abscesses FCE 22891 proved the most active agent in infections induced by methicillin susceptible and resistant Staphylococcus aureus while all three compounds were very active, against Str. pyogenes [12].
• The in-vitro and in-vivo activity of metronidazole and spiramycin, singly or in combination, was tested in the eradication of infection caused by Bacteroides spp. alone and in combination with Neisseria gonorrhoea, Staphylococcus aureus, Streptococcus pyogenes or Str. faecalis [13].

Biological context of Nsdhl

• Analysis of Nsdhl-deficient embryos reveals a role for Hedgehog signaling in early placental development [14].
• 0. Using a ubiquitously expressed, X-linked lacZ transgene that undergoes normal X-inactivation, we demonstrate that the placental defects in Nsdhl/+ female embryos are non-cell autonomous [14].
• Comparative genome sequence analysis of the Bpa/Str region in mouse and Man [15].
• Bpa and Str have been localized to an overlapping critical region of 600 kb that demonstrates conserved gene order with loci in human Xq28 between DXS1104 and DXS52 [16].
• Our analysis used gene prediction and a database search of 430 kb of genomic sequence covering the Bpa/Str region of the mouse X chromosome, and 745 kb of genomic sequence from the homologous human X chromosome region [15].

Anatomical context of Nsdhl

• Our results demonstrated that in Str mouse in addition to abnormal coat texture, sweat glands were severely dystrophic or missing [2].
• Similarly, lesions containing macrophages develop in striated muscle [8].
• By contrast, the muscle-type promoter is active in a wider range of cell types, including not only striated and smooth muscle, but also glial cells to a lesser extent, and probably neurons [17].
• Striated muscle fibres differentiate in monolayer cultures of adult thymus reticulum [18].
• Systemic gene transfer to striated muscles is hampered by the vascular endothelium, which represents a barrier to distribution of vectors via the circulation [19].

Associations of Nsdhl with chemical compounds

• Nsdhl is a 3beta-hydroxysterol dehydrogenase that is involved in the removal of C-4 methyl groups in the cholesterol biosynthetic pathway [20].
• Identification of two novel mutations in the murine Nsdhl sterol dehydrogenase gene and development of a functional complementation assay in yeast [20].
• These results indicate that cytosolic PLA2 and arachidonic acid regulate striated muscle growth by modulating multiple growth-regulatory pathways [21].
• Thus, varying levels of GLUT4 protein in striated muscle and adipose tissue can markedly alter whole body glucose disposal [22].
• Beta 1D integrin displaces the beta 1A isoform in striated muscles: localization at junctional structures and signaling potential in nonmuscle cells [23].

Physical interactions of Nsdhl

• Effects of streptozotocin-induced diabetes and physical training on gene expression of titin-based stretch-sensing complexes in mouse striated muscle [24].
• Sarcospan is an integral membrane component of the dystrophin-glycoprotein complex (DGC) found at the sarcolemma of striated and smooth muscle [25].
• Erythrocyte tropomodulin (E-Tmod) stabilizes short actin protofilaments in erythrocytes and caps longer sarcomeric actin filaments in striated muscles [26].

Co-localisations of Nsdhl

• PKC-epsilon-GFP bound with a striated pattern that co-localized with alpha-actinin, a marker of the Z-line of the sarcomere [27].

Regulatory relationships of Nsdhl

• Raf-1 transcripts of 3.1 kb were found to be expressed in all tissues examined with highest levels in striated muscle, cerebellum and fetal brain [28].
• Adhalin was specifically expressed in striated muscle cells and their immediate precursors, and absent in many other cell types [29].
• Deletion of cytosolic phospholipase A2 promotes striated muscle growth [21].
• The beta-enolase gene is expressed only in striated muscles [30].
• Murine Bcl-2 was light to moderately expressed in the latero-basal domain of cells of submandibular acini but was only lightly expressed in striated and eosinophilic ducts [31].

Other interactions of Nsdhl

• The consequences of enforced FasL expression in striated muscle is particularly controversial [32].
• Tropomodulin1 (Tmod1) caps thin filament pointed ends in striated muscle, where it controls filament lengths by regulating actin dynamics [33].
• Fxr1 knockout mice show a striated muscle phenotype: implications for Fxr1p function in vivo [34].
• The B isoform of creatine kinase (BCK), which is expressed at a high level in embryonic neural tissues, is also expressed abundantly in developing striated muscle and is an early marker for skeletal myogenesis [35].
• Merosin is the predominant laminin isoform in the basal lamina of striated muscle and peripheral nerve, and consists of M, B1 or S, and B2 chains [36].

Analytical, diagnostic and therapeutic context of Nsdhl

• Reverse transcriptase PCR (RT-PCR) and Northern analysis demonstrate that several of the transcripts are expressed in mid-gestation murine embryos and neonatal skin, making them candidates for the Bpa and Str mutations and their respective homologous human disorders [16].
• In the present study, we have investigated the subcellular localization of tagged proteins encoded by wild-type and selected mutant murine Nsdhl alleles using confocal microscopy [37].
• Here we show, using a ribonuclease protection assay, that the DMD gene is developmentally regulated in rat and mouse myogenic cell cultures, and that it is expressed in rat and mouse striated muscle, in mouse smooth muscle and in rat, mouse and rabbit brain [38].
• Immunofluorescence and immunoelectron microscopy studies revealed that myopalladin also colocalized with CARP in the central I-band of striated muscle sarcomeres [39].
• Dystrophin appears as a doublet on Western blots of skeletal and cardiac muscle, and as a single band of lower abundance in smooth muscle that corresponds most closely in molecular weight to the upper band of the striated muscle doublet [40].

References